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  • Huang HJ
  • Schechtman K
  • Askar M
  • Bernadt C
  • Mitter B
  • et al.
Transplantation. 2024 Mar 1;108(3):777-786 doi: 10.1097/TP.0000000000004841.
CET Conclusion
Reviewer: Mr Simon Knight, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion: This pilot study recruited lung transplant recipients at 2 sites, and randomised them to standard immunosuppression (Tac, MMF, Pred) or a belatacept-based regimen (Tac, Belatacept and pred). The hypothesis was that belatacept-based immunosuppression might reduce the incidence of donor-specific antibodies (DSA), leading to a reduction in the risk of chronic lung allograft dysfunction (CLAD). The study was stopped after recruitment of 27 patients due to 3 deaths in the belatacept arm. Causes of death varied – 2 patients died from COVID-19 infection, one from CLAD related to infection, one from PTLD, one from pulmonary embolus and one from haemothorax. The authors ascribe 4 of these deaths to viral infections. No differences were seen in incidence of CLAD or development of DSA. It is very difficult to interpret these results given the small numbers, but clearly the authors were correct in stopping the study and switching patients to standard immunosuppression. The relationship of four of the deaths to viral infection would suggest that the immunosuppressive regimen may have contributed, and in the absence of any detectable clinical benefit, the conclusion that this regimen is unsafe in lung transplant recipients seem justified.
Aims: This study aimed to evaluate the feasibility and inform the design of an RCT investigating the efficacy and safety of belatacept following lung transplantation
Interventions: Participants were randomly assigned to either continue standard-of-care immunosuppression or switch to belatacept.
Participants: 27 lung transplant recipients.
Outcomes: The primary outcome was to assess the feasibility of randomising 80% of eligible patients within 4 hours posttransplantation. The primary outcome was later changed to survival following the cessation of treatment with belatacept.
Follow Up: 1 year posttransplantation.
BACKGROUND:

Chronic lung allograft dysfunction (CLAD) is the leading cause of death beyond the first year after lung transplantation. The development of donor-specific antibodies (DSA) is a recognized risk factor for CLAD. Based on experience in kidney transplantation, we hypothesized that belatacept, a selective T-cell costimulatory blocker, would reduce the incidence of DSA after lung transplantation, which may ameliorate the risk of CLAD.

METHODS:

We conducted a pilot randomized controlled trial (RCT) at 2 sites to assess the feasibility and inform the design of a large-scale RCT. All participants were treated with rabbit antithymocyte globulin for induction immunosuppression. Participants in the control arm were treated with tacrolimus, mycophenolate mofetil, and prednisone, and participants in the belatacept arm were treated with tacrolimus, belatacept, and prednisone through day 89 after transplant then converted to belatacept, mycophenolate mofetil, and prednisone for the remainder of year 1.

RESULTS:

After randomizing 27 participants, 3 in the belatacept arm died compared with none in the control arm. As a result, we stopped enrollment and treatment with belatacept, and all participants were treated with standard-of-care immunosuppression. Overall, 6 participants in the belatacept arm died compared with none in the control arm (log rank P  = 0.008). We did not observe any differences in the incidence of DSA, acute cellular rejection, antibody-mediated rejection, CLAD, or infections between the 2 groups.

CONCLUSIONS:

We conclude that the investigational regimen used in this pilot RCT is associated with increased mortality after lung transplantation.

  • Manuel O
  • Laager M
  • Hirzel C
  • Neofytos D
  • Walti LN
  • et al.
Clin Infect Dis. 2024 Feb 17;78(2):312-323 doi: 10.1093/cid/ciad575.
CET Conclusion
Reviewer: Mr Simon Knight, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion: This multicentre trial enrolled kidney and liver transplant recipients receiving organs from CMV-positive donors, and randomised them to either fixed-duration prophylaxis, or guided by immune monitoring. In the study group, CMV ELISpot was used to monitor, and prophylaxis stopped if positive (indicating immune reactivity). The study failed to confirm non-inferiority of the immune monitoring strategy, although the overall rates of CMV infection were similar, with earlier CMV infection seen in the study group. However, duration of prophylaxis was shorter in the study arm. The failure to demonstrate non-inferiority is due to a lack of statistical power – in reality, the infection rates were very similar between groups. The study also fails to stratify randomisation by recipient serostatus, leading to an imbalance between the two arms of the study. This is important, as the risk of CMV infection is likely different between the two subgroups. Despite these limitations, it does appear that immune monitoring-guided prophylaxis is a reasonable strategy, resulting in a shorter duration of prophylaxis and a relatively low risk of clinically relevant CMV disease.
Aims: The aim of this study was to compare the effect of an immune monitoring–guided approach versus the current standard for tailoring the duration of antiviral prophylaxis to measure cytomegalovirus (CMV)-specific immunity in solid-organ transplant recipients.
Interventions: Participants were randomised to receive a duration of antiviral prophylaxis according to immune–guided monitoring or a fixed duration (control).
Participants: 193 kidney and liver transplant recipients CMV-seronegative with seropositive donors or CMV-seropositive receiving antithymocyte globulins.
Outcomes: The two primary endpoints were proportion of patients with clinically significant CMV infection and reduction in days of prophylaxis. The secondary endpoints were the incidence of all CMV events including untreated CMV replication, high-level CMV-DNAemia, patient survival, graft survival and incidence of acute rejection.
Follow Up: 1 year
BACKGROUND:

The use of assays detecting cytomegalovirus (CMV)-specific T cell-mediated immunity may individualize the duration of antiviral prophylaxis after transplantation.

METHODS:

In this randomized trial, kidney and liver transplant recipients from 6 centers in Switzerland were enrolled if they were CMV-seronegative with seropositive donors or CMV-seropositive receiving antithymocyte globulins. Patients were randomized to a duration of antiviral prophylaxis based on immune monitoring (intervention) or a fixed duration (control). Patients in the control group were planned to receive 180 days (CMV-seronegative) or 90 days (CMV-seropositive) of valganciclovir. Patients were assessed monthly with a CMV ELISpot assay (T-Track CMV); prophylaxis in the intervention group was stopped if the assay was positive. The co-primary outcomes were the proportion of patients with clinically significant CMV infection and reduction in days of prophylaxis. Between-group differences were adjusted for CMV serostatus.

RESULTS:

Overall, 193 patients were randomized (92 in the immune-monitoring group and 101 in the control group), of whom 185 had evaluation of the primary outcome (87 and 98 patients). CMV infection occurred in 26 of 87 (adjusted percentage, 30.9%) in the immune-monitoring group and in 32 of 98 (adjusted percentage, 31.1%) in the control group (adjusted risk difference, -0.1; 95% confidence interval [CI], -13.0% to 12.7%; P = .064). The duration of prophylaxis was shorter in the immune-monitoring group (adjusted difference, -26.0 days; 95%, CI, -41.1 to -10.8 days; P < .001).

CONCLUSIONS:

Immune monitoring resulted in a significant reduction of antiviral prophylaxis, but we were unable to establish noninferiority of this approach on the co-primary outcome of CMV infection.

CLINICAL TRIALS REGISTRATION:

NCT02538172.

  • Dellgren G
  • Lund TK
  • Raivio P
  • Leuckfeld I
  • Svahn J
  • et al.
Lancet Respir Med. 2024 Jan;12(1):34-44 doi: 10.1016/S2213-2600(23)00293-X.
CET Conclusion
Reviewer: Mr Keno Mentor, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion: Tacrolimus has largely replaced ciclosporin as the calcineurin inhibitor of choice for immunosuppression therapy in lung transplant patients in most countries. This is based on evidence, which the Cochrane group graded as low quality, suggesting reduced rates of chronic rejection associated with tacrolimus-based protocols. This randomised controlled trial was based in Scandinavia, where ciclosporin use is still preferred. 249 patients were randomised to either tacrolimus or ciclosporin-based immunosuppression regimes. The primary outcome was rates of chronic lung allograft dysfunction (CLAD), an umbrella term which encompasses a range of syndromes which cause lung graft failure and is predominantly a result of chronic rejection. The authors argue that this is a more clinically relevant measure than the pathology-based assessments used in other studies. Importantly, the clinical assessment of CLAD was based on committee consensus who were blinded to the treatment groups. The rate of CLAD in the tacrolimus group was significantly lower than the ciclosporin group, with lower rates of acute rejection and graft survival at 3 years. As is true in other organ groups, this well-designed study supports the existing evidence that tacrolimus should be the calcineurin inhibitor of choice in immunosuppression therapy after lung transplantation.
Aims: This study aimed to examine the effect of using tacrolimus once per day versus ciclosporin twice per day on the cumulative incidence of chronic lung allograft dysfunction (CLAD) at 36 months following transplantation in de novo lung transplant recipients.
Interventions: Participants were randomised to either the tacrolimus group or the ciclosporin group.
Participants: 264 adult patients (18–70 years) planning to to undergo a de novo double lung transplantation
Outcomes: The primary endpoint was the cumulative incidence of CLAD at 36 months post transplantation. The secondary endpoints were the composite measure of freedom from treated acute rejection and CLAD, and patient and graft survival following transplantation.
Follow Up: 36 months
BACKGROUND:

Evidence is low regarding the choice of calcineurin inhibitor for immunosuppression after lung transplantation. We aimed to compare the use of tacrolimus once per day with ciclosporin twice per day according to the current definition of chronic lung allograft dysfunction (CLAD) after lung transplantation.

METHODS:

ScanCLAD is an investigator-initiated, open-label, multicentre, randomised, controlled trial in Scandinavia evaluating whether an immunosuppressive protocol based on anti-thymocyte globulin induction followed by tacrolimus (once per day), mycophenolate mofetil, and corticosteroids reduces the incidence of CLAD after de novo lung transplantation compared with a protocol using ciclosporin (twice per day), mycophenolate mofetil, and corticosteroids. Patients aged 18-70 years who were scheduled to undergo double lung transplantation were randomly allocated (1:1) to receive either oral ciclosporin (2-3 mg/kg before transplantation and 3 mg/kg [twice per day] from postoperative day 1) or oral tacrolimus (0·05-0·1 mg/kg before transplantation and 0·1-0·2 mg/kg from postoperative day 1). The primary endpoint was CLAD at 36 months post transplantation, determined by repeated lung function tests and adjudicated by an independent committee, and was assessed with a competing-risks analysis with death and re-transplantation as competing events. The primary outcome was assessed in the modified intention-to-treat (mITT) population, defined as those who underwent transplantation and received at least one dose of study drug. This study is registered at ClinicalTrials.gov (NCT02936505) and EudraCT (2015-004137-27).

FINDINGS:

Between Oct 21, 2016, and July 10, 2019, 383 patients were screened for eligibility. 249 patients underwent double lung transplantation and received at least one dose of study drug, and were thus included in the mITT population: 125 (50%) in the ciclosporin group and 124 (50%) in the tacrolimus group. The mITT population consisted of 138 (55%) men and 111 (45%) women, with a mean age of 55·2 years (SD 10·2), and no patients were lost to follow-up. In the mITT population, CLAD occurred in 48 patients (cumulative incidence 39% [95% CI 31-48]) in the ciclosporin group and 16 patients (13% [8-21]) in the tacrolimus group at 36 months post transplantation (hazard ratio [HR] 0·28 [95% CI 0·15-0·52], log-rank p<0·0001). Overall survival did not differ between groups at 3 years in the mITT population (74% [65-81] for ciclosporin vs 79% [70-85] for tacrolimus; HR 0·72 [95% CI 0·41-1·27], log-rank p=0·25). However, in the per protocol CLAD population (those in the mITT population who also had at least one post-baseline lung function test allowing assessment of CLAD), allograft survival was significantly better in the tacrolimus group (HR 0·49 [95% CI 0·26-0·91], log-rank p=0·021). Adverse events totalled 1516 in the ciclosporin group and 1459 in the tacrolimus group. The most frequent adverse events were infection (453 events), acute rejection (165 events), and anaemia (129 events) in the ciclosporin group, and infection (568 events), anaemia (108 events), and acute rejection (98 events) in the tacrolimus group. 112 (90%) patients in the ciclosporin group and 108 (87%) in the tacrolimus group had at least one serious adverse event.

INTERPRETATION:

Immunosuppression based on use of tacrolimus once per day significantly reduced the incidence of CLAD compared with use of ciclosporin twice per day. These findings support the use of tacrolimus as the first choice of calcineurin inhibitor after lung transplantation.

FUNDING:

Astellas, the ALF-agreement, Scandiatransplant Organization, and Heart Centre Research Committee, Rigshospitalet, Denmark.

  • Toniato de Rezende Freschi J
  • Cristelli MP
  • Viana LA
  • Ficher KN
  • Nakamura MR
  • et al.
Transplantation. 2024 Jan 1;108(1):261-275 doi: 10.1097/TP.0000000000004749.
CET Conclusion
Reviewer: Mr Keno Mentor, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion: Mammalian target of rapamycin inhibitors (mTORi) have been increasingly investigated as alternate immunosuppression agents for kidney transplant patients to reduce the adverse effects of the current standard combination of mycophenolate and calcineurin inhibitor. Sirolimus and everolimus have distinct pharmacokinetic and pharmacodynamic properties and this trial sought to compare outcomes in kidney transplant patients utilising immunosuppression regimens based on each of these mTORi agents. A standard regimen group (mycophenolate/tacrolimus) was also included as a control. The primary outcome was the rate of CMV infection in the first year after transplantation. There were no significant differences in the rate of CMV infection nor in the secondary outcomes including BK virus infection, acute rejection and delayed graft function between the two mTORi agents. However, the study was limited by a small sample size and short follow-up period.
Aims: This study aimed to compare the outcomes of de novo sirolimus (SRL) versus everolimus (EVR) plus reduced-dose tacrolimus among renal transplant patients.
Interventions: Participants were randomised to one of three groups including the SRL group, the EVR group and the mycophenolate sodium (MPS) group.
Participants: 268 first kidney transplant recipients.
Outcomes: The primary outcome was the incidence of the first CMV infection/disease at 12 months posttransplantation. The secondary outcomes included BK polyomavirus (BKPyV) viremia, treatment failure, de novo donor-specific antibodies, 12-month protocol biopsies, kidney function and drug discontinuation.
Follow Up: 12 months
BACKGROUND:

Mammalian target of rapamycin inhibitors (mTORi), sirolimus (SRL) and everolimus (EVR), have distinct pharmacokinetic/pharmacodynamics properties. There are no studies comparing the efficacy and safety of de novo use of SRL versus EVR in combination with reduced-dose calcineurin inhibitor.

METHODS:

This single-center prospective, randomized study included first kidney transplant recipients receiving a single 3 mg/kg antithymocyte globulin dose, tacrolimus, and prednisone, without cytomegalovirus (CMV) pharmacological prophylaxis. Patients were randomized into 3 groups: SRL, EVR, or mycophenolate sodium (MPS). Doses of SRL and EVR were adjusted to maintain whole blood concentrations between 4 and 8 ng/mL. The primary endpoint was the 12-mo incidence of the first CMV infection/disease.

RESULTS:

There were 266 patients (SRL, n = 86; EVR, n = 90; MPS, n = 90). The incidence of the first CMV event was lower in the mTORi versus MPS groups (10.5% versus 7.8% versus 43.3%, P  < 0.0001). There were no differences in the incidence of BK polyomavirus viremia (8.2% versus 10.1% versus 15.1%, P  = 0.360). There were no differences in survival-free from treatment failure (87.8% versus 88.8% versus 93.3%, P  = 0.421) and incidence of donor-specific antibodies. At 12 mo, there were no differences in kidney function (75 ± 23 versus 78 ± 24 versus 77 ± 24 mL/min/1.73 m 2 , P  = 0.736), proteinuria, and histology in protocol biopsies. Treatment discontinuation was higher among patients receiving SRL or EVR (18.6% versus 15.6% versus 6.7%, P  = 0.054).

CONCLUSIONS:

De novo use of SRL or EVR, targeting similar therapeutic blood concentrations, shows comparable efficacy and safety. The reduced incidence of CMV infection/disease and distinct safety profile of mTORi versus mycophenolate were confirmed in this study.

  • Jandovitz N
  • George SJ
  • Abate M
  • Kressel AM
  • Bolognese AC
  • et al.
Clin Transplant. 2023 Dec;37(12):e15139 doi: 10.1111/ctr.15139.
CET Conclusion
Reviewer: Mr Keno Mentor, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion: This single-blinded randomised control trial investigated the potential benefit of continuous glucose monitoring (CGM) over the standard finger-prick glucose monitoring in diabetic patients in the first five days following kidney transplantation. 37 patients were randomised and included in the analysis. There were no significant differences in the outcomes of median glucose values or amount of insulin used across the five post-operative days. Secondary clinical outcomes of infection rates and length of hospital stay were also not significantly different between the two groups. This study thus did not produce compelling evidence for the use of CGM in this patient group, but larger studies with longer follow up periods may be needed to detect a meaningful effect.
Aims: This study aimed to compare continuous glucose monitoring versus conventional point-of-care finger-stick glucose monitoring for improving post-transplant glycemic control in renal transplant recipients.
Interventions: Participants were randomised to either receive conventional finger-stick glucose monitoring or continuous monitoring.
Participants: 40 adult renal transplant recipients.
Outcomes: The primary outcome was median daily glucose level. The secondary outcomes were number of hyperglycemic and hypoglycemic episodes, total insulin use, infection and hospital length of stay.
Follow Up: 5 days posttransplantation
INTRODUCTION:

This study examines whether the use of inpatient Continuous Glucose Monitors provides improved glycemic control over finger-stick glucose monitoring post-transplant.

METHODS:

This is a single-site, prospective randomized controlled trial of 40 patients receiving conventional finger-stick glucose monitoring or continuous monitoring using the Medtronic Guardian Sensor 3 during the first 5 days post-transplant. Included patients were adult renal transplant recipients with a diagnosis of diabetes. Assessed endpoints included post-transplant daily median glucose level, hyperglycemic (≥180 mg/dL) and hypoglycemic (≤80 mg/dL) episodes, number of post-transplant bacterial infections and length of stay.

RESULTS:

Groups were well matched in demographic variables. Median daily glucose was significantly lower in the intervention group. There were also significantly less episodes of hyperglycemia on postoperative days 2, 3, 4, and 5. There were no differences in the incidences of hypoglycemia, postoperative bacterial infections, or length of stay.

CONCLUSION:

In this randomized study, the use of a continuous glucose monitor to guide post-transplant glucose management significantly lowered the incidence of hyperglycemic episodes and median glucose levels through the first 5 days post-transplant without increasing the number of hypoglycemic episodes. The use of these devices can be considered in the immediate post-renal transplant setting.

  • O'Connor-Cordova MA
  • Ortega-Macias AG
  • Sancen-Herrera JP
  • Altamirano-Lamarque F
  • Del Toro AV
  • et al.
Transplant Rev (Orlando). 2023 Dec;37(4):100789 doi: 10.1016/j.trre.2023.100789.
CET Conclusion
Reviewer: Reshma Rana Magar, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion: This systematic review aimed compare the safety, feasibility, and outcomes of RAKT versus OKT. Study selection, quality assessment and data extraction were performed by two independent authors. Nine studies were included, all of which were cohort studies. The authors concluded that RAKT has significantly lower complication rate compared to OKT, without significant differences in terms of intraoperative, perioperative and postoperative outcomes. Heterogeneity was significant for some of the outcomes, which was not explored. Since only observational studies were included, it is possible that the results may have been influenced by selection bias and potential confounders.
Aims: The aim of this study was to compare the outcomes of living donor robotic-assisted kidney transplant (RAKT) versus traditional living donor open kidney transplant (OKT).
Interventions: Electronic databases including PubMed, Scopus, and Cochrane were searched. Study screening, evidence grading and data extraction were performed by two independent reviewers. Methodological quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS) for cohort studies.
Participants: 9 studies were included in the review.
Outcomes: Outcomes of interest included intraoperative outcomes (total procedure time, anastomoses time, total ischemia time, rewarming ischemia time, blood loss, blood transfusion and incision length), early postoperative outcomes (surgical site infection, symptomatic lymphocele rate, ileus, overall complications, Clavien-Dindo classification complication rate, hospital readmission rate, visual analogue pain score, creatinine 24 h posttransplant), and follow-up outcomes (patient survival 36 months posttransplant)
Follow Up: N/A
BACKGROUND:

Renal transplant is the standard of care for patients with end-stage renal disease (ESRD). Robotic-assisted kidney transplant (RAKT) has emerged as a safe minimally invasive approach with a lower complication rate than open kidney transplant (OKT). Concerns regarding ischemia times and graft function are still a matter of debate.

METHODS:

Following PRISMA guidelines and PROSPERO registration CRD42023413774, a systematic review was performed in March 2023 on RAKT compared to OKT. Primary outcomes of interest were surgical times, ischemia times, blood loss, complication rates, and graft function. Data were analyzed using R version 4.2.2.

RESULTS:

A total of nine studies comparing living donor RAKT to living donor OKT were included, totaling 1477 patients, out of which 508 underwent RAKT and 969 OKT. RAKT cases were highly selected as depicted in the manuscript. Cumulative analysis showed significantly longer total ischemic time (MD = 16.51; 95% CI = [9.86-23.16]) and rewarming ischemia time (MD = 11.24; 95% CI = [-0.46-22.01]) in RAKT group. No differences were found in total procedure time and time to complete anastomoses. Blood loss and transfusion rate were lower in RAKT group (MD = -53.68; 95% CI = [-89.78; -17.58]) and (RR = 0.29; 95% CI = [0.14; 0.57]), respectively. The meta-analysis revealed a lower rate of surgical site infection (SSI) (RR = 0.31; 95% CI = [0.19-0.52]) and symptomatic lymphocele (RR = 0.16; 95% CI = [0.06-0.43]) in RAKT. No difference in ileus rate was found. Pain scores were significantly lower in the RAKT group (MD = -1.14; 95% CI = [-1.59 - -0.69]; p ≤0.01). No difference in length of stay and hospital readmission were evidenced. Delayed graft function (DGF) and acute rejection rates were not different between interventions groups (RR =1.23; 95% CI = [0.40-3.74]) and (RR =0.96; 95% CI = [0.55-1.70]), respectively. No difference between groups in early graft outcomes are evident.

CONCLUSIONS:

Our analysis suggests that RAKT is a minimally invasive, safe, and feasible procedure. It is associated with a lower complication rate and similar intraoperative, perioperative, and postoperative outcomes. Further quality studies are needed to confirm these findings.

  • Haller J
  • Diebold M
  • Leuzinger K
  • Wehmeier C
  • Handschin J
  • et al.
Transplantation. 2023 Dec 1;107(12):2568-2574 doi: 10.1097/TP.0000000000004712.
CET Conclusion
Reviewer: Mr Simon Knight, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion: This post-hoc analysis of an RCT investigated the predictive value of urine CXCL10 levels in the diagnosis of BK viral replication. CXCL10 levels were associated with risk of viruria, presence of decoy cells and viraemia. Negative predictive value was high (96%) with an AUC of 0.79, although positive predictive value was low (21%) meaning that the test is not very specific. These findings suggest that urine CXCL10 monitoring may be a useful strategy to rule out significant BK virus infection in transplant recipients. It is worth noting that the investigators selected patients without recent acute rejection episodes, and the test is not specific enough to differentiate between rejection and BK viral infection, meaning that confirmatory tests would be required. The actual clinical benefit of CXCL10 monitoring would need to be confirmed in a prospective RCT.
Aims: This secondary analysis of a randomised controlled trial (RCT) aimed to assess levels of urine CXCL10 at different stages of BK polyomavirus (BKPyV) reactivation and to determine the predictive ability of urine CXCL10 for BKPyV replication.
Interventions: Participants in the original trial were randomly assigned to either the intervention arm where elevated levels of urine CXCL10 indicated the performance of a renal allograft biopsy with therapeutic adaptations based on the result; and the control arm, where the results of the urine CXCL10 analyses was concealed.
Participants: 235 adult kidney transplant recipients from the original trial were included.
Outcomes: The outcomes of interest included urine CXCL10 levels at different stages of BKPyV infection, urine CXCL10 levels at different phases of patients with BKPyV DNAemia and diagnostic performance of urine CXCL10 for detecting BKPyV replication.
Follow Up: 1 year
BACKGROUND:

Urine CXCL10 is a biomarker for renal allograft inflammation induced by rejection, urinary tract infection, or BK polyomavirus (BKPyV) replication. This study aimed to compare urine CXCL10 levels in different stages of BKPyV reactivation and to investigate urine CXCL10 as a biomarker for BKPyV replication.

METHODS:

We included 763 urine samples (235 patients) from an interventional, randomized trial obtained in the context of regular screening for urine CXCL10 levels. All urine samples had a complete urine sediment analysis, no rejection episode noted within 30 d before urine collection, and a urine decoy cell analysis was conducted within ±3 d.

RESULTS:

Urine CXCL10 levels were 2.31 ng/mmol in samples without BKPyV viruria, slightly rose to 4.35 ng/mmol with BKPyV viruria, and then markedly increased to 16.42 ng/mmol when decoy cells were detectable, but still in the absence of BKPyV DNAemia ( P  < 0.001). The highest urine CXCL10 values were observed in samples with BKPyV DNAemia (median 42.59 ng/mmol). The area under the curve of urine CXCL10 levels to detect ≥3 decoy cells was 0.816. At a CXCL10 cutoff of 3 ng/mmol, the negative predictive value was 97%. The area under the curve of urine CXCL10 levels to detect BKPyV DNAemia was 0.882, with a negative predictive value of 99% at a CXCL10 cutoff of 3 ng/mmol.

CONCLUSIONS:

Urine CXCL10 levels are already significantly elevated in BKPyV viruria (especially with decoy cell shedding) and further increase with BKPyV DNAemia. Low urine CXCL10 values can rule out the presence of ≥3 decoy cells and BKPyV DNAemia with high certainty.

  • Karar H
  • Shafiekhani M
  • Mahmoudi MM
  • Azadeh N
  • Shamsaeefar A
  • et al.
BMC Res Notes. 2023 Oct 26;16(1):295 doi: 10.1186/s13104-023-06568-9.
CET Conclusion
Reviewer: Mr Keno Mentor, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion: This non-blinded randomised study compared two techniques for arterial anastomosis of the pancreas graft in simultaneous pancreas/kidney (SPK) transplant. The standard technique involves using a ‘y-graft’ derived from the bifurcation of the common iliac into the internal and external iliac arteries, while the modified technique tested in this study uses this standard technique with the addition of an extension graft derived from donor carotid artery. 30 patients were randomised equally between the two groups with no significant differences found in the primary outcomes of post-operative thrombosis, pancreatitis and surgical site infection. Small patient numbers and a lack of analysis of important donor and graft confounding factors (e.g. donor age, cold ischaemic time, etc) mean these findings cannot be generalised.
Aims: The aim of this study was to examine whether a novel technique for arterial reconstruction improves post-surgical outcomes in SPK transplant receipts.
Interventions: Participants were randomised to receive either the the Y-graft technique or the Y-graft and extension technique.
Participants: 30 simultaneous pancreas-kidney transplant recipeints.
Outcomes: The main clinical outcomes of this study were incidence of the post-surgical complications (pancreatitis, vascular events, fistula formation, and rejection).
Follow Up: 3 months following transplantation
INTRODUCTION:

Simultaneous pancreas kidney (SPK) transplantation is an invaluable procedure to enhance the quality of life of insulin-dependent patients with advanced renal disease. The creation of vascular anastomoses of the donor's pancreas vessels to the recipient's, is of utmost importance to predict the graft outcome and surgical complications. In the study we introduce a novel technique for arterial reconstruction during SPK transplantation.

METHODS:

Conventionally, during the SPK transplantation, a so-called Y-graft is anastomosed between donor's superior mesenteric and splenic artery to the recipient's right iliac artery. In the study we adopted a new technique by preparing an extra extension using the donor's carotid artery, to be anastomosed to the Y-graft and the iliac artery. In this non-blinded randomized clinical trial we compared the surgical complications and early outcomes between the 2 groups of patients with the traditional and new arterial reconstruction techniques during 3 months after transplantation.

RESULTS:

Thirty adult patients were included in the study. The incidence of pancreatitis, vascular thrombosis and surgical site infection was lower in the new Y-graft and extension technique, which was not statistically significant. However, the calculated Cohen's d index showed the medium effect of new Y-graft and extension technique on complication after SPK transplantations.

CONCLUSION:

The post-operative complications tend to be lower in the novel arterial reconstruction technique, however a study on a larger patient group is encouraged to confirm our primary results.

TRIAL REGISTRATION:

The study was registered at the Iranian Registry of Clinical Trials on 12/05/2022; IRCT 20210625051701N2; ( http://www.irct.ir/ ).

  • Rasaei N
  • Malekmakan L
  • Gholamabbas G
  • Abdizadeh P
Exp Clin Transplant. 2023 Oct;21(10):814-819 doi: 10.6002/ect.2023.0071.
CET Conclusion
Reviewer: Mr Simon Knight, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion: This small single centre RCT randomised 16 kidney transplant recipients with BK viral infection to receive either IvIG alone, or IvIG in combination with leflunomide. BK viral loads decreased in both groups, with significantly lower viral levels in the leflunomide group. No difference in graft function was seen between groups. The main limitation of this study is the small sample size, with just 8 patients in each group. No a priori sample size calculation is presented. No adverse events/safety data are reported – only BK virus levels and serum creatinine data. Whilst this paper provides some rationale for a larger study, it is far from conclusive.
Aims: The aim of this study was to examine the therapeutic effect of the combination of intravenous immunoglobulin (IVIG) and leflunomide in comparison to IVIG alone for treating BK virus infection in kidney transplant recipients.
Interventions: Participants were randomised to receive either IVIG + leflunomide or IVIG alone.
Participants: 16 kidney transplant recipients with BK virus infection.
Outcomes: The main outcomes of interest were serum levels of the BK virus and creatinine levels.
Follow Up: 3 months
OBJECTIVES:

Nephropathy due to BK virus infection is a major cause of graft dysfunction and loss. No specific treatment has been developed for the BK virus. Here, we compared the combination of intravenous immunoglobulin and leflunomide versus intravenous immunoglobulin to treat BK virus nephropathy after renal transplant.

MATERIALS AND METHODS:

This study was a randomized controlled clinical trial. Sixteen kidney transplant patients with BK virus infection were randomly divided into 2 groups; 1 group received intravenous immunoglobulin, and another group received leflunomide and intravenous immunoglobulin. P < .05 was considered statistically significant.

RESULTS:

Results of a polymerase chain reaction test for BK virus after 2 months of treatment were negative in 3 patients in the intravenous immunoglobulin group and in 7 patients in the intravenous immunoglobulin + leflunomide group. The amount of BK virus decreased significantly in each group, and a significant difference was observed between the 2 groups after 3 months (P = .014). The average level of creatinine in the intravenous immunoglobulin group at 1, 2, and 3 months after treatment was 1.7 ± 0.23, 1.8 ± 0.5, and 1.5 ± 0.3, respectively, and in the intravenous immunoglobulin + leflunomide group was 2.1 ± 0.75, 1.76 ± 0.37, and 1.4 ± 0.18, respectively (P > .05).

CONCLUSIONS:

Although BK viral load decreased significantly in both groups, there was a significant difference between patients who received intravenous immunoglobulin versus those who received the combination of intravenous immunoglobulin + leflunomide after 3 months. The addition of leflunomide to the intravenous immunoglobulin treatment seems to have a better effect in reducing BK viral load. However, further studies with a larger sample and longer duration are needed.

  • Hosseinpour M
  • Pezeshgi A
  • Mahdiabadi MZ
  • Sabzghabaei F
  • Hajishah H
  • et al.
BMC Nephrol. 2023 Sep 27;24(1):284 doi: 10.1186/s12882-023-03338-4.
CET Conclusion
Reviewer: Reshma Rana Magar, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion: This systematic review aimed to determine the prevalence of UTIs and the risk factors that influence their development and progression. Twenty-six studies were included in the review. Apart from one randomised controlled trial and one case-control study, the rest were cohort studies. The study found that UTIs were a significant problem among kidney transplant recipients. Risk factors associated with an increased risk of UTI included history of UTIs, deceased donor, female, old age, long-term use of an indwelling catheter, acute rejection, diabetes, use of ureteral stent, abnormal anatomy of the urinary tract and hypertension. Heterogeneity between studies was significantly high, which the authors suspect could be due to differences in study procedures, follow-up time, UTI definition and healthcare systems. There is no mention of potential confounders that could have influenced the analyses.
Aims: This study aimed to explore the prevalence of urinary tract infection (UTI) and its associated risk factors among kidney transplant recipients.
Interventions: A literature search was conducted on PubMed, Medlib, ScienceDirect, ISI, Scopus, and Embase. Two independent reviewers were involved in the study selection process. The Newcastle–Ottawa checklist was used to assess the quality of the included studies.
Participants: 26 studies were included in the review.
Outcomes: The main outcomes of interest were prevalence of UTIs and risk factors associated with UTIs in patients following kidney transplant.
Follow Up: N/A
BACKGROUND:

A kidney recipient's urinary tract infection (UTI) can result in infectious problems and be a risk factor for less successful transplant outcomes. UTI risk factors are still controversial. The present study aimed to investigate the prevalence of UTI and its association with risk factors in kidney recipients.

METHOD:

Twenty-six papers published between 2005 and 2022 were retrieved using keywords and searching Medlib, ScienceDirect, PubMed, and other databases. If possible, the pooled prevalence of UTI in kidney recipients and odds ratio (OR) with a 95% confidence interval for each risk factor were calculated. The data were analyzed using the random effects model in R and Stata 14.

RESULTS:

The total sample size was 72,600, with an average age of 48.7 years. The pooled prevalence of UTI was 35% (95% CI, 30-40%). The estimated risk factors for UTI were female (OR = 3.13; 95%CI: 2.35-4.17), older age (OR = 1.03; 95%CI: 1-1.05), history of UTI (OR = 1.31; 95%CI) CI: 1.05-1.63), receiving a kidney from a deceased donor (OR = 1.59; 95%CI: 1.23-2.35), long-term use of an indwelling catheter (OR = 3.03; 95%CI: 1.59-6.59), a ureteral stent (OR = 1.54; 95%CI: 1.16-2.06), diabetes (OR = 1.17; 95%CI: 0.97-1.41), hypertension (OR = 1.6; 95%CI: 1.26-2.28), acute rejection process (OR = 2.22; 95%CI: 1.45-3.4), and abnormal urinary tract anatomy (OR = 2.87; 95%CI 1.44-5.74).

CONCLUSION:

This meta-analysis revealed that UTIs are a significant problem in kidney recipients. Factors such as female sex, old age, history of UTIs, deceased donor, long-term use of an indwelling catheter, diabetes, acute rejection process, use of ureteral stent, abnormal urinary tract anatomy, and hypertension were related to an increased risk of UTIs in kidney recipients.